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Objective:To explore the clinical and histopathologic features of lupus nephritis (LN) patients with positive antineutrophil cytoplasmic antibody (ANCA), so as to provide more theoretical basis to recognize and treat this disease.Methods:Clinical data of biopsy-proven LN patients with ANCA test in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2002 to September 11, 2020 were collected and analyzed retrospectively. The difference of clinical data, laboratory examination, and pathological examination of renal biopsy between ANCA-positive group and ANCA-negative group. The clinicopathological characteristics between different ANCA serotypes were compared.Results:A total of 1 304 patients with LN confirmed by renal biopsy and ANCA test results were enrolled. Eighty ANCA-positive patients from 1 304 LN patients were screened. There are 55(68.8%) ANCA-positive LN patients with positive anti-myeloperoxidase antibodies (MPO). There were 14(17.5%) ANCA-positive LN patients with positive anti-proteinase 3 antibodies (PR3), and 11(13.8%) ANCA-positive patients with double positive antibodies of MPO and PR3. ANCA-positive LN patients had significantly higher serum creatinine [135.5(68.0, 361.8) μmol/L vs 88.0(64.0, 165.0) μmol/L, P=0.004] and blood urea nitrogen [12.35(6.35, 21.18) mmol/L vs 8.60 (5.50, 15.70) mmol/L, P=0.026] as well as lower estimated glomerular filtration rate [45.70(13.83, 84.10) ml·min -1·(1.73 m 2) -1 vs 66.75(38.43, 96.22) ml·min -1·(1.73 m 2) -1, P=0.001] than ANCA-negative patients (stratified sampling of 160 patients). ANCA-positive LN patients had higher chronicity index than ANCA-negative LN patients [3(2, 7) vs 2(0, 5), P=0.006]. There were statistically significant difference in hemoglobin, serum creatinine and estimated glomerular filtration rate among ANCA-positive group, ANCA-negative group, and MPO-ANCA and PR3-ANCA double positive group. MPO-ANCA and PR3-ANCA double positive LN patients had the lowest hemoglobin and estimated glomerular filtration rate, and highest serum creatinine among the three groups (all P<0.05). Conclusions:ANCA-positive LN patients have worse renal function and higher renal histological chronicity index than ANCA-negative LN patients, especially for patients with double positive MPO-ANCA and PR3-ANCA. More stringent monitoring and therapy may be needed in this subgroup of LN patients.
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Objective:To report a rare case of paroxysmal nocturnal hemoglobinuria (PNH) complicated with chronic tubulointerstitial nephropathy, combined with literature review, and discuss the clinical, imaging and pathological characteristics of the disease and the diagnosis and treatment ideas.Methods:The patient's clinical data, magnetic resonance imaging (MRI) and kidney pathological examination results, treatment measures and effects were collected and reported. Through systematic review of relevant literature, the clinical manifestations and pathogenesis of chronic tubular interstitial nephropathy complicated by PNH were summarized and discussed.Results:In this case, PNH was diagnosed for more than 30 years, the peripheral blood PNH clone was positive, urine specific gravity was 1.012, urine pH 6.0-7.0, urine protein (+), urine sugar (3+), serum creatinine 259 μmol/L, serum lactic acid dehydrogenase 800 U/L. MRI showed bilateral renal cortical signal was low intensity on both T1- and T2- weighted images. Kidney biopsy revealed remarkable chronic tubulointerstitial nephropathy with massive hemosiderin deposition in proximal tubular cells demonstrated by Prussian blue staining and electron microscopy. By using low-dose prednisone to control hemolytic attack and other supportive treatments, the patient's renal function has been stabilized for a long time.Conclusions:PNH complicated with chronic tubulointerstitial nephritis is easy to be misdiagnosed due to insidious onset. MRI and kidney histopathological examination are helpful to clarify the diagnosis. Early diagnosis and treatment are helpful to improve the prognosis of such patients.
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Objective@#To investigate the effect of construction of trauma care center on the treatment of patients with severe multiple trauma.@*Methods@#A retrospective case control study was conducted to analyze the clinical data of 412 patients with severe multiple trauma admitted to the First Affiliated Hospital of Soochow University from December 2015 to November 2017. There were 250 males and 162 females, aged 19-80 years [(45.8±15.9)years]. The injury severity score (ISS) ranged from 18 to 57 points [(28.2±9.3)points]. The observation group included 211 patients who were treated after the establishment of the provincial trauma treatment center in Jiangsu Province, and the control group included 201 patients who were treated before the establishment of the provincial trauma treatment center. The durations from arrival to the start of rescue, from consultation to completion of CT examination, from applying for blood transfusion to the execution of blood transfusion by nurses, the time of stay at the resuscitation room and the mortality rate were compared between the two groups.@*Results@#The observation group presented better results in the durations from arrival to the start of rescue [(2.5±1.7)minutes vs. (5.4±2.6)minutes], from the start of the rescue to completion of CT scan [(36.2±11.6)minutes vs. (53.2±12.9)minutes], the transfusion time [(28.7±11.3)minutes vs. (46.5±14.1)minutes], and the time of stay at resuscitation room [(3.0±2.0)hours vs. (5.0±2.8)hours] (P<0.05 or 0.01). The mortality rate in the observation group was 3.8% (8/211), which was significantly lower than 8.5% (17/201) in control group (P<0.05).@*Conclusion@#The construction of trauma treatment center can effectively shorten the treatment time of patients with severe multiple trauma, reduce the mortality rate and improve the efficacy, which is worthy of promotion.
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Objective To investigate the effect of construction of trauma care center on the treatment of patients with severe multiple trauma.Methods A retrospective case control study was conducted to analyze the clinical data of 412 patients with severe multiple trauma admitted to the First Affiliated Hospital of Soochow University from December 2015 to November 2017.There were 250 males and 162 females,aged 19-80 years [(45.8 ±15.9)years].The injury severity score (ISS) ranged from 18 to 57 points [(28.2 ±9.3)points].The observation group included 211 patients who were treated after the establishment of the provincial trauma treatment center in Jiangsu Province,and the control group included 201 patients who were treated before the establishment of the provincial trauma treatment center.The durations from arrival to the start of rescue,from consultation to completion of CT examination,from applying for blood transfusion to the execution of blood transfusion by nurses,the time of stay at the resuscitation room and the mortality rate were compared between the two groups.Results The observation group presented better results in the durations from arrival to the start of rescue [(2.5 ±1.7) minutes vs.(5.4 ± 2.6) minutes],from the start of the rescue to completion of CT scan [(36.2 ±11.6) minutes vs.(53.2 ± 12.9) minutes],the transfusion time [(28.7 ± 11.3) minutes vs.(46.5 ±14.1) minutes],and the time of stay at resuscitation room [(3.0 ± 2.0) hours vs.(5.0 ± 2.8) hours](P＜0.05 or 0.01).The mortality rate in the observation group was 3.8％ (8/211),which was significantly lower than 8.5％ (17/201) in control group (P ＜ 0.05).Conclusion The construction of trauma treatment center can effectively shorten the treatment time of patients with severe multiple trauma,reduce the mortality rate and improve the efficacy,which is worthy of promotion.
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Objective@#To investigate the roles and anti-cancer mechanism of artificially synthesized EGF-containing fibulin-like extracellular matrix protein (EFEMP1) derived tumor suppressor ZR30 protein in glioma (GBM).@*Methods@#ZR30 protein were in vitro expressed using a wheat germ cell-free system. GBM cell lines (U251, U251NS, and U87) were cultured for 2-3 days in the presence or absence of ZR30 treatment. MMP-2 level was detected by gelatin zymography assay, moreover, the expression of EGFR, Notch-1 and p-Akt/Akt levels were determined by western blot. Additionally, MTT assay was used to measure ZR30′s effect on the cell proliferation of U251 and U251NS cells. Furthermore, pre-mixed U251-GFP and U251NS-RFP cells (1∶9) were injected into the brain of nude mice, and then ZR30 or PBS was injected into the intra-tumor after 10 and 21 days, respectively. Then DNA was extracted from the right brain of nude mice in each group. Comparative quantitative polymerase chain reaction (CQ-PCR) was used to examine the copy numbers of human gene hSPAG16, mouse gene mSpag16, GFP and RFP. The survival status of each group of nude mice was also observed.@*Results@#The levels of activated MMP-2 in U87 and U251 cells were lower after 10, 50 and 100 ng/ml ZR30 treatment for 2-3 days. Western blot analysis showed that ZR30 treatment reduced the expression of EGFR, Notch-1 and p-Akt/Akt in U251 cells, and inhibited Notch-1 and p-Akt/Akt expression in U251NS cells, and then decreased the response of U251 cells to EGF stimulation. Moreover, ZR30 inhibited the cell proliferation of U251 and U251NS two days after exposure. The in vivo orthotopic GBM xenografts were successfully constructed. CQ-PCR results indicated that the hSPAG16/mSpag16 ratios of mice in PBS group and ZR30 treatment groups at 180, 700, and 1 800 ng dosages were 3.67±2.82, 1.18±0.97, 1.75±1.55 and 1.38±1.17, respectively, and ZR30 treatment groups showed significantly lower ratios than the PBS group (P<0.05 for all). Correspondingly, the ratios of GFP/RFP in each group were 1.97±0.80, 1.97±0.85, 1.48±0.71 and 1.73±0.77, respectively, showing no statistical significance (P>0.05 for all). When treatment was performed 10 d after cell implantation, and the median survival time of mice in PBS group and ZR30 group was 40.5 days and 59.0 days, respectively. When treatment was performed 21 d after cell implantation, the median survival time of mice in PBS group and ZR30 group was extended to 57.0 days and 74.5 days, respectively. The median survival time of ZR30 treatment groups significantly prolonged (P<0.05 for all).@*Conclusions@#ZR30 inhibits in vitro cell growth, invasion, angiogenesis and stemness maintenance in glioma via suppressing activated MMP-2, EGFR, p-Akt/Akt and Notch-1 proteins. In vivo, ZR30 markedly increased survival of mice harboring glioma xenografts, even for only one intra-tumoral injection at the time of early tumor formation. Overall, the in vivo and in vitro experiments supported the therapeutic potential of ZR30 for GBM.
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AIM: To investigate the role of reactive oxygen species (ROS) in transforming growth factor-?1 (TGF-?1)-induced regulation of plasminogen activator inhibitor-1 (PAI-1) expression and plasmin activity. METHODS: Growth arrested and synchronized rat mesangial cells were stimulated by TGF-?1. In some experiments,cells were pretreated with BSO or with antioxidant NAC. Intracellular ROS production was visualized using a fluorescent dye. PAI-1 protein secretion by mesangial cells was measured by Western blot and PAI-1 mRNA by both RT-PCR and Northern blot. Plasmin activity was determined using a synthetic fluorometric plasmin substrate. RESULTS: Exogenous TGF-?1 significantly increased intracellular ROS concentration and upregulated PAI-1 mRNA and protein expression in mesangial cells and reduced the plasmin activity. TGF-?1-induced upregulation of PAI-1 mRNA expression was exaggerated by BSO[DL-buthionine-(S,R)-sulfoximine]. NAC (N-acetylcysteine) effectively reversed TGF-?1-induced PAI-1 mRNA overexpression and plasmin activity decreasing. CONCLUSION: TGF-?1 increases intracellular ROS generation. ROS acts as a signaling molecular to mediate TGF-?1-induced PAI-1 overexpression and decrease in plasmin activity.
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Objective To explore the role of ROS in TGF ?1 induced changes of plasmin system in rat mesangial cells. Methods Growth arrested and synchronized rat mesangial cells were stimulated by 2 ng/ml TGF ?1 for 12 h. In some experiments cells were pretreated with BSO for 24 h or with antioxidant NAC for 1h. Intracellular ROS production was visualized using a fluorescent dye.The mRNA expression of tPA, uPA and PAI 1 was measured by RT PCR and PAI 1 protein secreted into media by ELISA assay.The activities of plasmin, uPA, tPA were determined using a synthetic fluorometric substrate. Results TGF ?1 significantly increased intracellular ROS concentration. 2 ng/ml TGF ?1 significantly upregulated PAI 1 mRNA and protein expression by 1 9 fold(P